S-triazinylmethyl ureas



United States Patent 2,993,897 a s-TRIAZINYLMETHYL UREAS Seymour L. Shapiro, Hastings on Hudson, and Louis Freedmam'Bi-onxville, N.Y,, assignors to U. S. Vitamin & Pharmaceutical Corporation, a corporation of Delaware No Drawing. {Filed Apr. 15, 1960, Ser. No. 22,414 6 Claims. (Cl. 260-2493) This invention is concerned with novel triazine derivatives, and particularly s-triazinylmethyl ureas, of the structure:

48-96 hrs. the reaction mixture is quenched by decantation into water and the formed product is separated and purified by recrystallization; k

The compounds of this invention show useful pharmacological properties, particularly as anti-convulsant agents, analgesics and anti-inflammatory agents. The compounds are weak bases and accordingly, salts with strong mineral acids such as hydrochloric, hydrob romic, and the like may be formed.

The process and compounds of this invention will be more clearly understood from a consideration of the following specific examples which are given for the purpose of illustration only and are. not to be construed as limiting the scope of the invention in any way.

EXAMPLE 1 2 amino 4 anilino 6 (ureidomethyl) s triazine-A solution of 7.3 g. (0.05 mole) of ethyl hydantoate in ml. of methanol was treated with 8.9 g. (0.05 mole) of phenylbiguanide and the reaction stored at 20 for '4 days. The reaction mixture was added to 50 ml. of water and the product (1.65 g.) was separated. recrystallization (dimethylformamide-ether) yielded 1.44 g. (11%) of product which melted at 227 dec.

EXAMPLE 2 In a similar manner and using the appropriate biguanide, the triazinylmethyl ureas prepared have been tabulated.

Table Analyses, percent d N 0. R1 M.P., 0. 8 Formula Carbon Hydrogen Nitrogen Calcd. Fd Calcd. Fd. Oalcd. Fd.

1 CaH5- 202-303 (1. A O8H13N'l0 43. 0 43. 1 5. 1 5. 8 43.9 44. 4 2 (s) 231 d. A 10H17N70 47. 8 48.1 6. 8 7. 1 3* n... CgHaOHz- 183-184 B O13H19N1O2L- 51. 1 52. 1 6. 3 6. 3 4 09H5CH1CH2..- 204-205 d. A Gully/N10 34. l 33. 8 O 227 d. O 51.0 51. 4 5.1 5. 0 37. 8 37. 6 238 d. B 52. 7 53. 2 5. 5 5. 9 35. 9 36. 3 209-211 (1. B 52. 7 52. 2 5. 5 5. 4 35. 9 35. 5 247-248 d. B 54. 3 54. 3 6. 0 6. 0 34. 1 34. 4 213-214 (1. B 55. 8 55. 4 6.4 6. 1 2,6-diOHaCgHa. 250 d. A 54. 3 53. 7 6.0 5. 9 34.1 34. 2 2-C1G9H4- 169 D 33. 4 33. 1 O C 257 d. A OnHnC1N70 45.0 44. 9 4. 1 3. 7 33. 4 33. 5 295 d A. O11H12B1N7O 39. 1 39. 9 3. 6 3. 6 29.0 28. 5 3-BrOflH4- 218 d A OuHnBrN-1O- 39. 1 39. 5 3. 6 3. 8 29. 0 28. 6 4-CH3O O H 216-217 B OnHusN'IOz. 49. 8 50. 1 5. 2 5. 0

' R2=H unless otherwise indicated.

b Melting points are not corrected.

Recrystallizlug solvent: A=dimethylformamide+aeetonitrile; B=dimethylformamide; O=dimethy1- formamide+ether; D=acetonitrile.

4 Analyses by Weller and Strauss, Oxford, Engalnd.

OBHB 1S allyl. Isolated as a hydrate. K R1R2N'-iS piperidino.

(E. M. Smolin and L. Rapoport, s-Triazines and Derivatives, Interscience Publishers, New York, N.Y., 1959, p. 56, 236) which have the ureido group or groups at tached directly to the triazine nucleus.

The compounds are prepared by reaction of ethyl hydantoate with a substantially equivalent quantity of the biguanide in a solvent such as methanol, and after a suitable reaction period desirably at about 20 and over For therapeutic purposes the compounds of this invention are formulated to contain 20-200 mg. of active ingredient in a pharmaceutical extender which does not co-act with the active principles described herein.

It is to be understood that it is intended to cover all changes and modifications of the examples herein chosen for the purposes of illustration which do not constitute departures irom the spirit and scope of the invention.

3 4 We claim: 2. The compound of claim 1, wherein R is phenyl and 1. The compound R is hydrogen.

NH: 3. The compound of claim 1, wherein R is o-chlorophenyl and R is hydrogen. N 5 4. The compound of claim 1, wherein R is benzyl and R i! R2 is methyl.

NK 5. The compound of claim 1, wherein R is o-bromo- N/ ll phenyl and R is hydrogen.

2 6. The compound of claim -1, wherein R is phenyl and wherein (a) R is selected from the group consisting of 10 R is methyl.

lower alkyl, lower aralkyl, phenyl, and substituted phenyl wherein said substituents are selected from the group References Clted 111 the file of 11115 132mmt consisting of lower alkyl, lower alkoxy, chloro and bromo,

R is selected from the group consisting of hydrogen and UNITED STATES PATENTS lower alkyl, and wherein (b) R +R is pentamethylene. 15 2,394,042 DAlelio Feb. 5, 1946 

1. THE COMPOUND 